Mechanisms of ellipticine-mediated resistance in UKF-NB-4 neuroblastoma cells
| Autor: | Marie Stiborová, Jitka Poljaková, Jan Hraběta, Jana Hřebačková, Zuzana Zemanova, Tomas Eckschlager, Antonin Libra, Martin Bunček, Pavel Prochazka |
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| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
Cellular respiration Antineoplastic Agents Apoptosis Real-Time Polymerase Chain Reaction Flow cytometry Neuroblastoma Downregulation and upregulation Cell Line Tumor medicine Humans Ellipticines In Situ Hybridization Fluorescence Oligonucleotide Array Sequence Analysis Comparative Genomic Hybridization biology medicine.diagnostic_test Reverse Transcriptase Polymerase Chain Reaction Topoisomerase General Medicine medicine.disease Flow Cytometry Molecular biology Blot Oncology Proto-Oncogene Proteins c-bcl-2 Drug Resistance Neoplasm Cancer research biology.protein Efflux DNA Topoisomerases |
| Zdroj: | Cancer science. 103(2) |
| ISSN: | 1349-7006 |
| Popis: | Most high-risk neuroblastomas develop resistance to cytostatics and therefore there is a need to develop new drugs. In previous studies, we found that ellipticine induces apoptosis in human neuroblastoma cells. We also investigated whether ellipticine was able to induce resistance in the UKF-NB-4 neuroblastoma line and concluded that it may be possible after long-term treatment with increasing concentrations of ellipticine. The aim of the present study was to investigate the mechanisms responsible for ellipticine resistance. To elucidate the mechanisms involved, we used the ellipticine-resistant subline UKF-NB-4ELLI and performed comparative genomic hybridization, multicolor and interphase FISH, expression microarray, real-time RT-PCR, flow cytometry and western blotting analysis of proteins. On the basis of our results, it appears that ellipticine resistance in neuroblastoma is caused by a combination of overexpression of Bcl-2, efflux or degradation of the drug and downregulation of topoisomerases. Other mechanisms, such as upregulation of enzymes involved in oxidative phosphorylation, cellular respiration, V-ATPases, aerobic respiration or spermine synthetase, as well as reduced growth rate, may also be involved. Some changes are expressed at the DNA level, including gains, amplifications or deletions. The present study demonstrates that resistance to ellipticine is caused by a combination of mechanisms. (Cancer Sci 2012; 103: 334–341) |
| Databáze: | OpenAIRE |
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